The heart arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF) progenitors. Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors (MCPs) common for both heart fields. However, it remains unclear whether at the single cell level, Mesp1 progenitors represent a common progenitor for the FHF and SHF. Using mosaic tracing and inducible clonal analysis with a multicolor reporter strategy, we investigated the contribution of Mesp1 cardiovascular progenitors in a temporally controlled manner during the early gastrulation. Our data indicated that the myocardium derives from ~250 Mesp1 expressing cardiac progenitors born during gastrulation. Temporal analysis of clonally labeled Mesp1 cells revealed the existence of temporally distinct populations of Mesp1 progenitors that are restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Moreover biophysical analysis of clonal data revealed that, despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. Altogether, these results provide insights into the number of cardiac progenitors and their mode of growth. Moreover they provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors expressing Mesp1 independently at different time points during gastrulation. Our data reveal that the regional segregation and lineage restriction of cardiac progenitors occurs very early during embryonic development. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

<p>Despite its lack of septation, the tissue patterning of the arterial pole of the zebrafish is remarkably similar to the patterning of pulmonary and aortic arterial poles observed in mouse and chick. The secondary heart field (SHF) is a conserved developmental domain in avian and mammalian embryos that contributes myocardium and smooth muscle to the cardiac arterial pole. This field is part of the overall heart field, and its myocardial component has been fate mapped from the mesoderm to the heart in both mammals and birds. In this study I demonstrate that the population that gives rise to the arterial pole of the zebrafish can be traced from the epiblast, is a discrete part of the mesodermal heart field. This zebrafish SHF contributes myocardium after initial heart tube formation, giving rise to both smooth muscle and myocardium. I show that this field expresses Isl1, a transcription factor associated with the SHF in other species. I further show that differentiation, induced by Bmp signaling, occurs in this progenitor population as cells are added to the heart tube. Some molecular pathways required for SHF development in birds and mammals are conserved in teleosts, as Nkx2.5 and Nkx2.7 as well as Fgf8 regulate Bmp signaling in the zebrafish heart fields. Additionally, the transcription factor Tbx1 and the Sonic hedgehog pathway are necessary for normal development of the zebrafish arterial pole.</p> / Dissertation